Markers of Long-Term Suppression of HIV in Pre-adolescents treated from Infancy

描述（由申请人提供）：在早期治疗的儿童中，HAART导致一种独特的病毒持续状态，在这种状态下，HIV复制完全由抗逆转录病毒药物控制，几乎没有HIV特异性免疫（精英治疗应答者）。我们假设，长期早期有效的婴儿治疗可能会促进HIV持续状态，这与长期治疗的成人不同，后者由可忽略不计的前病毒DNA水平、不可检测的静止CD4+T细胞潜伏复制能力病毒库、无残留病毒血症、HIV特异性免疫反应、免疫激活和炎症组成。在PHACS/AMP研究的背景下，我们将在青春期前儿科长期精英治疗应答者队列中测量以下指标：1)确定早期HAART对围产期HIV感染前青少年和从婴儿期开始接受治疗的青少年体内HIV病毒库大小和复制能力的长期影响；2)检查早期HAART对围产期HIV感染前青少年和青少年体内HIV病毒持续动态和免疫结果的长期影响；3)确定早期HAART治疗对青春期前和婴儿期开始治疗的青少年HIV病毒库多样性和复制能力的长期影响。拟议的项目将改善关于早期HAART对婴儿的长期病毒学和免疫学影响的科学知识，这些婴儿现在可能存活到青年期，并为在旨在实现儿童和青少年艾滋病毒治愈的临床试验中定义艾滋病毒治愈提供一个关键框架。

DESCRIPTION (provided by applicant): In early-treated children, HAART leads to a unique state of viral persistence whereby HIV replication is controlled solely by antiretroviral drugs wit little HIV-specific immunity (elite-treatment responders). We hypothesize that long-term early effective therapy of infants may promote a state of HIV persistence that is distinct from long-term treated adults that is comprised of negligible levels of proviral DNA, a nondetectable resting CD4+T cell latent replication-competent viral reservoir, absent residual viremia, HIV specific immune responses, immune activation and inflammation. In the context of the PHACS/AMP study, we will measure the following in a cohort of preadolescent pediatric long-term elite treatment responders: 1) Determine the long- term effects of early HAART on the size of proviral and replication-competent HIV reservoirs in perinatally HIV- infected pre-adolescents and adolescents treated from infancy, 2) Examine the long-term effects of early HAART from infancy on the dynamics of HIV persistence and immune outcomes in perinatally HIV-infected pre-adolescents and adolescents, and 3) Determine the long-term effect of early HAART on diversity of proviral and replication-competent HIV reservoirs in pre-adolescents and adolescents treated from infancy. The proposed project will improve scientific knowledge on the long-term virologic and immunologic effects of early HAART for infants who are now likely to survive to young adulthood and provide a critical framework for defining HIV CURE in clinical trials aimed at achieving HIV CURE for children and adolescents.